The goal of this application is to develop a multidisciplinary Center for the Analysis of Cellular Mechanisms and Systems Biology, to provide new infrastructure to advance understanding of cellular mechanisms, to better understand how to overcome disease, and to build a critical mass of faculty in this area. The Center will be unique in Montana and the five surrounding states, and will include a combination of capabilities for analysis of cellular mechanisms. This project will create a powerful Mass Spectrometry and Proteomics Core infrastructure, oriented toward training researchers. Most cellular mechanisms appear to be controlled by protein post-translational modifications and the MS and Proteomics Core will add: a high resolution Qtof MS for improved bottom up characterization of protein post-translational modifications, an FTMS for top-down characterization of modifications on intact proteins, a Hyperspectral imager for enhanced multicolor proteomic multiplexing to pin-point proteins that change with biological stimulation, and a protein electro-elution system for high efficiency recovery of pin-pointed proteins. Sensitive differential protein detection capabilities developed at MSU and high sensitivity microfluidic nano LC/MS/MS will be included in the Core. New software will integrate data from an existing DNA microarray Facility. A Proteomics Reagent Synthesis Core will prepare new fluorescent reagents for differential analysis of changes in enzyme activity and post-translational modifications, that result from biological stimulation. We will build critical mass by first supporting the development of three young faculty and one senior faculty member, who is charting a new course in his research. Outstanding local and national mentors and External Advisory Committee members will guide the development of these faculty and the Center. Second, we will hire four new faculty in areas needed to build critical mass: a Chemical Biologist/Organic Synthesis expert, a Biological Mass Spectroscopist using advanced FTMS tools, a Systems Biologist working on metabolic modeling and metabolomics, and a Cell Biologist using global molecular tools. Outstanding MSU Institutional Support ($1,400,000), the significance and timeliness of the post-genomic analysis of cellular mechanisms, and the orientation toward training in advanced methods will seed new projects-and will result in significant scientific contributions and a sustainable Center.